UPMC Physician Resources

Breakthrough in HIV/AIDS Research Gives Hope for Improved Drug Therapy

PITTSBURGH, May 16, 2014 – The first direct proof of a long-suspected cause of multiple HIV-related health complications was recently obtained by a team led by the University of Pittsburgh Center for Vaccine Research (CVR). The finding supports complementary therapies to antiretroviral drugs to significantly slow HIV progression.

The study, which will be published in the June issue of the Journal of Clinical Investigation and is available online, found that a drug commonly given to patients receiving kidney dialysis significantly diminishes the levels of bacteria that escape from the gut and reduces health complications in non-human primates infected with the simian form of HIV. The study was funded by the National Institutes of Health (NIH).

“We now have direct evidence of a major culprit in poor outcomes for some HIV-infected people, which is an important breakthrough in the fight against AIDS,” said Ivona Pandrea, M.D., Ph.D., professor of pathology at Pitt’s CVR. “Researchers and doctors can now better test potential therapies to slow or stop a key cause of death and heart disease in people with HIV.”

Chronic activation of the immune system and inflammation are major determinants of progression of HIV infection to AIDS, and also play an important role in inducing excessive blood clotting and heart disease in HIV patients. Doctors believed this was due to microbial translocation, which occurs when bacteria in the gut gets out into the body through intestinal lining damaged by HIV.  However, no direct proof of this mechanism existed.

Dr. Pandrea and her colleagues showed blocking the bacteria from leaving the intestine reduces the chronic immune activation and inflammation. They did this by giving the drug Sevelamer, also known by the brand names Renvela and Renagel, to monkeys newly infected with simian immunodeficiency virus, or SIV, the primate-form of HIV.

Sevelamer is an oral drug approved by the U.S. Food and Drug Administration to treat elevated levels of phosphate in the blood of patients with chronic kidney disease.

The gut bacteria bind to Sevelamer, making it much more difficult for the bacteria to escape into the body and cause serious problems, such as heart disease, while further weakening the immune system and allowing HIV to progress to full-blown AIDS.

In SIV-infected monkeys treated with Sevelamer, levels of a protein that indicates microbial translocation remained low. However, in the untreated monkeys the levels increased nearly four-fold a week after SIV infection.

The treated monkeys with the lower rates of microbial translocation also had lower levels of a biomarker associated with excessive blood clotting, showing that heart attacks and stroke in HIV patients are more likely associated with chronic immune system activation and inflammation, rather than HIV drugs.

“These findings clearly demonstrate that stopping bacteria from leaving the gut reduces the rates of many HIV comorbidities,” said Dr. Pandrea.

Because most interventions in people infected with HIV begin after the person has reached chronic stages of infection when the gut is already severely damaged, Dr. Pandrea notes, “These treatments may not be as effective later in the infection. Clinical trials in HIV-infected patients were not yet successful in reducing microbial translocation in chronically infected patients. Our study points to the importance of early and sustained drug treatment in people infected with HIV.”

Other approaches, such as coupling Sevelamer with antibiotics, anti-inflammatory drugs, probiotics or supplementation of existing HIV/AIDS drugs could further reduce the likelihood of microbial translocation. Clinical trials are underway to assess these strategies.

Additional researchers on this study are Jan Kristoff, B.A., M.S., George Haret-Richter, Ph.D., Dongzhu Ma, Ph.D., Cuiling Xu, Ph.D., Jennifer L. Stock, B.S., Tianyu He, B.S., Adam D. Mobley, B.S., Samantha Ross, B.A., M.S., Anita Trichel, D.V.M., Ph.D., Cristian Apetrei, M.D. Ph.D., all of Pitt; Alan Landay, Ph.D., Rush University; Ruy M. Ribeiro, Ph.D., Los Alamos National Laboratory; Elaine Cornell, technician, and Russell Tracy, Ph.D., both of the University of Vermont; and Cara Wilson, M.D., of the University of Colorado.

This work was supported by NIH grants R01 HL117715, R01 RR025781, 5P01 AI076174 and P30 AI082151.

Magee Hosts Russian Physicians to Study Women’s Health

PITTSBURGH, May 15, 2014 – A delegation of five Russian obstetric gynecologists will visit Magee-Womens Hospital of UPMC and Magee-Womens Research Institute (MWRI) for a comprehensive program exploring advanced care practices and scientific research for a wide range of women’s health issues.

The delegation will spend May 23 to 31 in Pittsburgh learning best practices in gynecological care, obstetrics, neonatology, mid-wifery, maternal/fetal care and prenatal care. They also will learn about significant research advances in ovarian cancer, breast cancer, fertility, reproductive biology and uterine prolapse. Members of the delegation will shadow physicians and nurses in Magee’s neonatal intensive care unit, birth center and breast imaging center, and spend time in MWRI’s laboratories observing current research projects and technology.

“The visit from this delegation is an exciting opportunity to share medical and research advances happening in Pittsburgh that could have an impact nationally and internationally,” said Leslie Davis, president, Magee-Womens Hospital of UPMC. “It also is a wonderful chance for our researchers and physicians to learn from their Russian counterparts.”

The delegation is hosted by Magee Womancare International (MWI), a nonprofit organization that serves as the international humanitarian outreach arm of Magee.

“While our organization now brings health education programs and technical assistance to the international communities of Pittsburgh, we were first established to improve health care conditions for women and infants in the former Soviet Union,” said Nicole Travis, the administrative director of MWI. “The arrival of this delegation brings our work full circle, and we are greatly looking forward to sharing our resources here in Pittsburgh.”

This visit is managed by the Open World Leadership Center, a support agency of the United States Congress. The Open World program enhances understanding and capabilities for cooperation between the United States and the countries of Eurasia by developing a network of leaders in the region who have gained significant, firsthand exposure to American democracy and the free-market system.

For more information, please contact Nicole Travis at 412-641-8996 or travisn@mwri.magee.edu or Maura Sheldon, Open World Public Affairs Officer, at 202-707-6197.

Children’s Hospital of Pittsburgh of UPMC Study Shows Rise in Emergency Department Visits for Traumatic Brain Injury

PITTSBURGH, May 13, 2014 – There was a nearly 30 percent increase in the rate of visits to United States’ emergency departments (ED) for traumatic brain injury (TBI) from 2006 to 2010, according to a study led by a Children’s Hospital of Pittsburgh of UPMC physician. The rise might be attributable to a number of factors, including increased awareness and diagnoses.

Results of the study, led by Jennifer R. Marin, M.D., M.Sc., an emergency medicine physician at Children’s Hospital, are published in the recent issue of the Journal of the American Medical Association.

The team used data from the Nationwide Emergency Department Sample (NEDS) database to determine national trends in ED visits for TBI from 2006 through 2010. NEDS is a nationally representative database and includes 25 to 50 million visits from more than 950 hospitals each year. Additionally, the authors used U.S. census data in order to determine incidence rates and the burden of traumatic brain injury on the U.S. population.

“The reason for this increase may be because more people are sustaining head injuries, patients are more aware of TBI and more likely to seek emergency care, health care professionals are more vigilant about making these diagnoses, or a combination of these,” said Dr. Marin, also assistant professor of pediatrics and emergency medicine at University of Pittsburgh School of Medicine. “The findings underscore the need for more evaluation into why and how to reverse these trends so that we can minimize the incidence of traumatic brain injury and the consequences associated with these injuries.”

The team found that in 2010 there were an estimated 2.5 million ED visits for TBI, representing a 29 percent increase in the rate of visits for TBI during the study period. By comparison, total ED visits increased by 3.6 percent. The majority of the increase in the incidence of TBI occurred in visits coded as concussion or unspecified head injury. Children younger than 3 years and adults older than 60 years had the largest increase in TBI rates. The majority of visits were for minor injuries and most patients were discharged from the ED.

“Traumatic brain injury is an important cause of morbidity and mortality each year,” Dr. Marin said. “There has been widespread attention to traumatic brain injury, specifically in terms of prevention, in the last decade by policy makers and health professionals. Large-scale studies that assess national statistics and trends are one of the few ways we have to understand the scope of the problem.”

The authors suggest that the increase in TBI among the very young and very old may indicate these age groups do not benefit as much from public health interventions, such as concussion and helmet laws and safer sports’ practices.

For more information on Dr. Marin and Children’s Hospital of Pittsburgh of UPMC, visit www.chp.edu.

UPMC Physicians Implant Pennsylvania’s First Wireless Pacemaker

PITTSBURGH, May 13, 2014 – UPMC electrophysiologists are the first in the state to implant a catheter-delivered, leadless pacemaker to treat life-threatening bradycardia, a slow heartbeat that reduces blood flow to the brain and body.

The Medtronic Micra Transcatheter Pacing System is a wireless device that detects a slow heartbeat and sends impulses to the heart to maintain a normal rhythm. The procedure was performed at UPMC Shadyside in mid-April on an 86-year-old man as part of the Medtronic Micra Transcatheter Pacing trial. UPMC is one of only six U.S. centers selected for participation in the international trial for patients who need a pacemaker. The device was the ninth implantation of the novel leadless pacemaker in the U.S.

Traditional pacemakers use a pulse generator unit that is implanted under the skin, usually in the upper chest, with one or more wires, known as leads, which are threaded through the veins to the right-side heart chambers. The miniaturized, leadless pacemaker is implanted directly into the right ventricle of the heart, gaining access via the femoral vein in the groin.

“One advantage compared to traditional pacemakers is that no incision is required. That can help reduce infection complications. This pacemaker eliminates the need for a lead, which is more prone to failure over time than any other part of the pacemaker system,” said Andrew Voigt, M.D., assistant professor, University of Pittsburgh School of Medicine, lead surgeon for the procedure and electrophysiologist at the UPMC Heart and Vascular Institute. “This minimally invasive approach simplifies the implantation procedure, does not require sutures or cause the appearance of a scar, and may improve patient satisfaction.”

In the U.S., the Medtronic Micra Transcatheter Pacing System will not be commercially available until the successful completion of this clinical trial and approval by the U.S. Food and Drug Administration. The trial is seeking to establish the safety and efficacy of this novel, miniaturized pacemaker system.

Pitt Receives $10 Million Grant from NIMH for Conte Center Focused on Schizophrenia

PITTSBURGH, May 8, 2014 – The National Institute of Mental Health (NIMH), part of the National Institutes of Health, has awarded a $10 million, five-year grant to establish the Silvio O. Conte Center for Translational Mental Health Research at the University of Pittsburgh School of Medicine’s Department of Psychiatry. The Center focuses on cortical cells, brain circuits, neuronal connectivity and cognition in schizophrenia.

Schizophrenia is a major public health problem and devastating illness, affecting 0.5 to 1 percent of the world’s population. Symptoms can include hallucinations, delusions, disorganized thinking and mood disturbances. Current treatments for schizophrenia have limited effectiveness, and all medications currently used to treat schizophrenia and related disorders were discovered by serendipity rather than goal-oriented, rigorous science.

“There is an urgent need for a new approach to treatment development to address these problems,” said David A. Lewis, M.D., UPMC Professor in Translational Neuroscience, chair of Pitt’s Department of Psychiatry, and director of the Conte Center. “This innovative Center will initiate drug development methodically by first identifying molecular targets that could influence the course of the illness, a strategy that has been successful in other areas of medicine.”

The Center’s research activities will test the hypothesis that molecular disturbances in certain triangular-shaped “pyramidal” cells, which are found in the outer layers of the brain’s cerebrum known as the neocortex, alter cortical circuitry within and between brain regions, impair functional connectivity and neural signaling, and disturb the processes of working memory and attention in individuals with schizophrenia.

Five research projects and clinical and diagnostic cores will take convergent approaches to examine these molecular changes with the aim of making laboratory findings readily relevant to clinical treatment of schizophrenia. The Center’s work is directed at identifying pathophysiology-based molecular targets for new treatments and at developing biomarkers that can be used to monitor their impact.

Center investigators include scientists from Pitt’s School of Medicine and the Dietrich School of Arts and Sciences, as well as Carnegie Mellon University, who represent a broad array of expertise spanning molecular systems and cognitive, computational and clinical neuroscience.

Research Study Available for Older Adults Living with Low Back Pain and Depression

PITTSBURGH, May 8, 2014 – Older adults experiencing chronic low back pain and depression are invited to participate in the final year of a five-year study that aims to find out whether medication alone or medication along with health coaching and learning new problem-solving skills is best for treating both conditions. The “Addressing Depression and Pain Together,” or ADAPT study, is an effort led by researchers at the University of Pittsburgh School of Medicine.

Both low back pain and clinical depression are common in seniors, and up to 25 percent of older adults suffer from both conditions at the same time, said principal investigator Jordan F. Karp, M.D., associate professor of psychiatry, University of Pittsburgh School of Medicine.

“Chronic low back pain and depression make each other worse, have similar risk factors, and increase the likelihood of each other’s recurrence,” he said. “Both can cause poor sleep and subsequent daytime drowsiness, keep people from participating or enjoying their usual activities, and isolate them at home. When they are both present, patients can enter a vicious cycle of the blues, pain, physical deconditioning, and feeling hopeless.”

For the ADAPT study, adults 60 or older who have depression symptoms and  low back pain on most days for at least three months will participate in the first stage during which everyone takes  the anti-depressant drug venlafaxine, also known as Effexor. Participants who have not improved after the first six weeks then have the opportunity to continue in the study for an additional 14 weeks, and be randomly assigned to receive a higher dose of venlafaxine alone or in combination with a counseling program that teaches problem-solving skills specific for managing pain, mood, sleep, and other difficulties commonly experienced by seniors living with these linked conditions.

At low doses, venlafaxine increases the levels of the neurotransmitter serotonin, which regulates mood. At higher doses, the drug also increases levels of the neurotransmitter norepinephrine, which regulates both mood and pain, Dr. Karp said.

“Venlafaxine has been approved for the treatment of anxiety and depression, and it is a widely used, well-tolerated drug,” he said. “Getting people moving and in better control of their pain through healthy behavior changes also may help their mood and improve quality of life.”

According to Dr. Karp, the goal of the study is to learn whether people who do not improve with low-dose venlafaxine alone need the addition of the problem-solving therapy to get them feeling better.

For more information about participating in the study, which is sponsored by the National Institutes of Health, call 412-246-6015 or visit www.ADAPTstudy.com.

Children’s Hospital of Pittsburgh of UPMC Researcher Receives Prestigious Research Award

PITTSBURGH, May 5, 2014 – The Academic Pediatric Association (APA) has awarded Alejandro Hoberman, M.D., chief, Division of General Academic Pediatrics at Children’s Hospital of Pittsburgh of UPMC, its 2014 APA Research Award. The award will be presented today at the Pediatric Academic Societies (PAS) annual meeting in Vancouver, British Columbia, Canada.

The award acknowledges his contributions toward advancing pediatric knowledge through excellence in research, originality, creativity and methodological soundness. Dr. Hoberman is known for his research on acute otitis media (AOM) and urinary tract infections (UTI).

The quality and influence of Dr. Hoberman’s research is evident from the journals in which they are published, including the New England Journal of Medicine (NEJM), Journal of the American Medical Association (JAMA), JAMA Pediatrics, and Pediatrics. He has served on the National Institutes of Health (NIH) special emphasis panels, NIH strategic planning workgroups, American Academy of Pediatrics guideline committees, and as a member of the Clinical and Translational Science Award Child Health Oversight Committee.

Dr. Hoberman graduated from medical school in Buenos Aires, Argentina, where he completed a general pediatrics residency at the Children’s Hospital of Buenos Aires. He then came to the United States for fellowship training in ambulatory pediatrics at Children’s Hospital of Pittsburgh under Jack L. Paradise, M.D., and Kenneth Rogers, M.D. Immediately following the fellowship, he joined the faculty at the University of Pittsburgh School of Medicine and Children’s Hospital of Pittsburgh of UPMC, and currently leads the Division of General Academic Pediatrics. In 2000, Dr. Hoberman was named the first Jack L. Paradise, M.D., Professor of Pediatric Research at Children’s.

“Everything goes back to what I learned from Dr. Paradise, who received the APA Research Award 20 years ago,” Dr. Hoberman said. “I remember watching him take great care with research participants to conduct a careful examination, and sitting with families to discuss clinical findings and how we were trying to learn how to provide better, evidenced-based care for their children and future generations of children. That personal touch and connection with families, which Dr. Paradise taught by example, enables trust and the understanding that the research team will always have the participant’s best interest in mind and provide the most comprehensive and careful medical care.”

“It was apparent soon after Dr. Hoberman’s arrival at Children’s that he had great promise,” said Jack L. Paradise, M.D., Professor Emeritus of Pediatrics, University of Pittsburgh School of Medicine. “He has more than met expectations, conducting important research while at the same time building one of the country’s strongest divisions of academic general pediatrics and serving as a role model for pediatric trainees at all levels. He richly deserves this prestigious award.”

In addition to receiving the award in Vancouver, Dr. Hoberman presented the results of his multi-center study showing how prophylactic antibiotics prevent urinary tract infection recurrences in children with vesicoureteral reflux.

For more information on Dr. Hoberman and Children’s Hospital of Pittsburgh of UPMC, visit www.chp.edu.

Children’s Hospital of Pittsburgh of UPMC Expert Shows Prophylactic Antibiotics Prevent Urinary Tract Infection Recurrences in Children with Vesicoureteral Reflux

VANCOUVER, BRITISH COLUMBIA, CANADA, May 4, 2014 – A study led by researchers at Children’s Hospital of Pittsburgh of UPMC demonstrated that children diagnosed with an abnormal flow of urine from the bladder to the upper urinary tract, called vesicoureteral reflux (VUR), can avoid recurrent urinary tract infections (UTI) by taking daily low-dose antibiotics, although the treatment didn’t reduce their risk for UTI-induced kidney scarring. The results of the multi-center study will be presented today at the Pediatric Academic Societies (PAS) annual meeting in Vancouver, British Columbia, Canada. The study also is published in the New England Journal of Medicine.

“Our study provides a clear message that recurrences of UTI in children with vesicoureteral reflux can be prevented, some of these children appear pretty sick when they have a UTI with fever,” said Alejandro Hoberman, M.D., chief, Division of General Academic Pediatrics at Children’s Hospital of Pittsburgh. “VUR is present in one-third of children presenting with UTI accompanied by a fever and has been associated with a heightened risk of kidney scarring. One way to decrease infection risk is to give children antibiotics when they are well, called antimicrobial prophylaxis.”

Earlier randomized, controlled trials that compared anti-reflux surgery with antimicrobial prophylaxis showed no differences in rates of recurrent UTIs and renal scarring; however, the actual efficacy of either treatment could not be determined because the studies lacked a placebo or observation comparison groups. Recently conducted randomized trials have reported conflicting results about the effectiveness of antimicrobial prophylaxis in reducing recurrences.

“This study showed unequivocal evidence that antimicrobial prophylaxis reduced at least in half the likelihood of children having recurrent UTIs,” said Dr. Hoberman, also professor of pediatrics at the University of Pittsburgh School of Medicine. “Some subgroups of children derived the most benefit, particularly those with bladder and bowel dysfunction at baseline, and those in whom the UTI occurred with fever.”

The goal of the two-year study was to determine if giving children low-dose trimethoprim-sulfamethoxazole would prevent recurrent UTIs, decrease kidney scarring and contribute to the emergence of bacterial resistance.

The study, named the Randomized Intervention for Children with Vesicoureteral Reflux (RIVUR) Trial, enrolled 607 children ages 2 to 71 months who were diagnosed with VUR following a first or second episode of UTI. Participants were recruited from 19 clinical trial centers in the United States and underwent kidney scans to determine if scarring was present. They were then randomized to receive trimethoprim-sulfamethoxazole or a placebo. Kidney scans were repeated at one and two years after study entry.

Results showed that 39 of 302 children (13 percent) receiving antimicrobial prophylaxis developed UTIs compared to 72 of 305 (24 percent) receiving placebo. Antimicrobial prophylaxis reduced the risk of infections by 50 percent compared with placebo.

“Rates of renal scarring at the outcome visit were low and not reduced by prophylaxis, perhaps because most children were enrolled after their first infection and because parents, instructed to be vigilant, sought early medical attention,” said Dr. Hoberman. “Not unexpectedly, recurrences that did occur in children who received prophylaxis were more likely to have been caused by a resistant pathogen.”

This research was supported by grants U01 DK074059, U01 DK074053, U01 DK074082, U01 DK074064, U01 DK074062, U01 DK074063 from the National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Department of Health and Human Services. This trial also was supported by the University of Pittsburgh Clinical and Translational Science Award (UL1RR024153 and UL1TR000005) and the Children’s Hospital of Philadelphia Clinical and Translational Science Award (UL1TR000003) both from the National Center for Research Resources, now at the National Center for Advancing Translational Sciences, National Institutes of Health.

For more information on Dr. Hoberman and Children’s Hospital of Pittsburgh of UPMC, visit www.chp.edu.

UPMC Physician Reaches Rare Milestone with 3000th Prostate Surgery

PITTSBURGH, May 1, 2014 Joel B. Nelson, M.D., chair of the Department of Urology at UPMC, has performed 3,000 radical prostatectomies since coming to Pittsburgh in 1999. He joins only a handful of surgeons in the world to reach this milestone.

Prostate cancer is the second most common cancer in American men, after skin cancer, with several treatments available for the disease. But often men shy away from surgical treatment because they believe it will leave them incontinent and impotent. Nerve-sparing radical prostatectomy is one of the most effective treatments because the cancer can be removed without harming nerves that control erections.

“The nerve-sparing approach not only removes the cancer but lowers the risk of impotence and bladder control problems, providing a better quality of life for the patient,” said Dr. Nelson. “Our vast experience distinguishes us from other programs and that helps give patients peace of mind when they seek treatment.”

Dr. Nelson has gained considerable recognition for both his clinical work and research. He has been featured in several publications due to the great strides he has made in the treatment of prostate cancer and is the recipient of multiple awards.

“We have seen remarkable results over the past decade. Currently, about 95 percent of patients undergo a bilateral nerve-sparing procedure with a prostate cancer-specific survival rate of 99.3 percent at five years and 98 percent at 10 years,” Dr. Nelson said.

Dr. Nelson also serves on the editorial boards for several scientific journals, including The Journal of Urology, and is an ad hoc reviewer for several other medical publications, including The New England Journal of Medicine.

UPMC East to Become Newest Site for UPMC Rehabilitation Institute

PITTSBURGH, May 1, 2014 – Construction is set to begin today on a new, 20-bed UPMC Rehabilitation Institute that is scheduled to open July 1 on the remodeled 6 East wing at UPMC East. It will mark the first Rehabilitation Institute location in Pittsburgh’s east-northeast corridor, complementing the current east-southeast location at UPMC McKeesport.

The facility will mark the ninth UPMC Rehabilitation Institute location as part of the system’s in-hospital network that provides specialized inpatient care for people needing physical, occupational and speech therapy after strokes or brain injuries, spinal cord injuries, various surgeries and other conditions. Children’s Hospital of Pittsburgh of UPMC also opened a Rehabilitation Institute this past winter. UPMC St. Margaret reopened its refurbished rehab unit in November, doubling its capacity to 26 beds.

“We are meeting a community need, in the area where our patients live,” said Mark Sevco, president of UPMC East. “It’s very exciting for us to open this in the eastern suburbs under the inpatient care of the Rehabilitation Institute. Utilizing existing space in a hospital that is very much in growth mode, just short of celebrating its second birthday, is a positive step for us. We continue to move forward with new clinical care.”

UPMC East recently was accredited by the independent Joint Commission as a primary stroke center. Stroke patients are expected to be among those receiving care at its new Rehabilitation Institute. Peter Hurh, M.D., specialist in inpatient rehabilitation and assistant professor in the Department of Physical Medicine and Rehabilitation at the University of Pittsburgh School of Medicine, will serve as the medical director of the new UPMC East location. This Rehabilitation Institute will bring at least 15 new hires to the community, among them full-time nurses, therapists, care managers, liaisons and more.

“There clearly is a need for more quality in-hospital rehabilitation units,” said Dr. Hurh. “We hope to address that need by opening this new unit at UPMC East, and bringing the Rehabilitation Institute’s experience and expertise to the eastern suburbs and beyond.”

“In the past year, we opened 12 new beds at a remodeled UPMC St. Margaret unit, Children’s came on line, and now we’re launching this new unit at UPMC East,” said Tim Kagle, executive director, UPMC Rehabilitation Network. “UPMC is growing in rehabilitation and showing both clinical quality and community success providing the care that people want and need in the neighborhoods and the areas where they live.”

Construction is considered to be relatively simple, hence it is scheduled to require barely two months. The primary focus of the work will entail the transformation of the waiting room, known as The Wedge, into a therapy gym, where such new equipment as a Lite Gait – a body-weight supporting gait system – will be part of the therapeutic curriculum. A multi-purpose room also will become the Activities for Daily Living unit.

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